维格列汀调控PKC-η及PKC-ζ表达以改善2型糖尿病大鼠肾功能的研究

Vildagliptinc regulated PKC-η and PKC-ζ expression improving renal function of type 2 diabetes in rats

目的:分析维格列汀干预2型糖尿病大鼠后,大鼠肾脏病理学、肾功能、血脂、PKC-η以及PKC-ζ治疗前后的变化特点。方法:将60只雄性SD大鼠随机分为空白组(control group,CG)、高脂饮食组(high fat group,HFG)以及维格列汀治疗组(vildagliptin group,VG),每组20只。HFG、VG给予高脂高糖饮食6个月建立2型糖尿病大鼠模型,模型建立成功后VG给予维格列汀57 mg·kg-1·d-1灌胃治疗,HFG给予相应生理盐水灌胃,CG不给予任何干预。分别在治疗4周和8周后处死大鼠各半,收集血清及肾脏行相关指标学检测。结果:大鼠肾脏切片HE染色可见,CG清晰无损伤;HFD在有一定的炎症反应,属于肾脏损害初期;治疗4周后VG即有明显变化,治疗8周后VG与CG基本一致。VG与HFG相比,治疗4周后血尿素、血肌酐、血尿酸、血尿素氮、总胆固醇、甘油三酯、低密度脂蛋白胆固醇明显降低(P<0.05),治疗8周后数值基本与治疗4周后一致,HDL-C治疗后没有改变;治疗4周后肾脏中PKC-η以及PKC-ζmRNA和蛋白表达明显降低(P<0.05),治疗8周后进一步降低,但变化不明显。结论:维格列汀可调节大鼠血脂,进而改善2型糖尿病大鼠肾功能,这可能与其降低肾脏中PKC-η以及PKC-ζ表达有关。

Objective： To investigate renal function,lipid and the expression of PKC-η and the PKC-ζ in vildagliptin treated type 2 diabetic rats. Methods： SD rats were randomly divided into control group（ CG）,high fat group（ HFG） and vildagliptin groups（ VG）,each group had 20. HFG and VG was given high-fat diet for 6 months to establish type 2 diabetic rat model,VG were orally given vildagliptin 57 mg · kg- 1· d- 1half rats were sacrificed,and their serum was collected for kidney related tests respectively after 4 and 8 weeks of treatment.Results： After treatment the kidney slices were HE stained,CG group was clear from any damage,and HFD group had some inflammation,but not obvious glomerular lesions. Vildagliptin can significantly improve the regulation of renal; function rea,creatinine,uric acid,TG and LDL-C,VG compared with HFG was significantly lower; vildagliptin could obviously treated and mitigate its PKC-η and PKC-ζ mRNA and protein expression. Conclusions： Vildagliptin can improve lipid metabolism thereby improving renal function in kidney of type 2diabetic rats via decreasing PKC-η and PKC-ζ expression.